Type 2 diabetes (T2D) and associated complications are major contributors to the global disease burden. T2D is already a major health threat in populations in developed countries and is rapidly taking hold in the developing world.

It is believed that understanding the complex interplay between genetic and lifestyle characteristics in the etiology of T2D and related complications will lead to the development of better preventive and therapeutic strategies. In Addition, the results of this project will facilitate our understanding of causes of diabetes in African Americans, other US and world populations

Objectives:

To conduct a genome-wide association study (GWAS) to identify susceptibility genetic variants for diabetes among the Yoruba people in Ibadan, Nigeria.

On the following day, perform confirmatory blood glucose for the small subset of participants requiring confirmation of previous test result DNA extraction of stored samples will be done at either the National Institutes of Health or the laboratory in Nigeria.

GWAS will be conducted using publicly available software packages.

Detailed Description

This research protocol is designed to study the genetic basis of Type 2 Diabetes (T2D) in a broad range of populations in the United States and abroad. This project takes advantage of the well established infrastructure and success of Dr. Rotimi s international genetic epidemiology study of T2D funded as an R01 grant by NIDDK while he was at Howard University. This parent project is ongoing in four major ethnic groups in Nigeria (Yoruba and Ibo) and Ghana (Akan and Gaa). At completion in 2013 and given current projections, we anticipate enrolling about 2,000 cases and 2000 controls from the five centers in West Africa (Enugu, Ibadan and Lagos in Nigeria; Accra and Kumasi in Ghana). However, current projection indicates that the enrollment of Yoruba cases and controls will be short by about 300 cases and 300 controls. It is critically important to supplement the enrollment of Yoruba participants from another community in the Ibadan metropolitan area in Nigeria. Therefore, the original goal of the current project is to enroll additional 300 cases of T2D and 300 ethnically matched Yoruba controls to facilitate the conduct of genome-wide association study (GWAS) and candidate gene/loci studies in West Africans. Other current and future projects will increase the number of subjects for future genome-wide association studies (GWAS), linkage disequilibrium (LD) mapping, and functional studies in different ethnically-defined populations. Each project will aim to enroll ethnically balanced cases and controls with the goal of facilitating the conduct of GWAS and candidate gene/loci studies in a broad range of populations. Overall, these studies aim to further (or in some cases be the first) such large-scale efforts to understand the genetic basis of T2D in individuals of varying backgrounds including African and Mexican ancestries. Identified candidate genes/loci will be investigated by re-sequencing and functional studies will be conducted to identify susceptibility variants for diabetes and associated complications including obesity, hypertension, nephropathy, neuropathy and retinopathy. Additionally, these samples will be used to study genetic variation in the context of how participants of different ancestry respond to drugs and other environmental factors and how this variation may have shaped population history. Given past activities, it is also anticipated that this resource will form the basis of multiple collaborations between Dr. Rotimi s lab, several NIH intramural researchers and non-NIH scientists. Each subsequent population that is added to this study over time will use the same procedures that were originally approved for ongoing work among West Africans.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Recruiting

Estimated Enrollment ICMJE

9000

Completion Date

Not Provided

Primary Completion Date

Not Provided

Eligibility Criteria ICMJE

INCLUSION CRITERIA:

Cases Men and women with confirmed type 2 diabetes mellitus that are either on treatment for diabetes or newly diagnosed with blood sugar reading on more than one occasion exceeding or equal to 126 mg/dl. These persons must be above the age of 25 years. In this regard, all newly diagnosed participants will be required to visit the clinic on the following day to perform a fasting blood glucose test to confirm previous results.

Controls Men and women with fasting plasma glucose (FPG) less than 100 mg/dl (5.6 mmol/l). Controls must be above age 25 years and should be ethnically matched to the cases. Enrolled cases and controls have to be unrelated. Therefore, only one person may be enrolled from each family unless they are husband and wife.

Attempts will be made to enroll an equal number of men and women. To ensure that ethnic distribution is maintained in each study, we are proposing to enroll ethnically-matched participants relevant to each study.

EXCLUSION CRITERIA:

People who do not meet the above criteria (e.g., younger than 24, without the blood sugar requirements, etc). No more than one non-spouse member of each family. No prisoners, pregnant women or fetuses will be included in this study.